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SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study.

Abstract：

BACKGROUND:The mechanism behind poor survival of acute myeloid leukemia (AML) patients with 1-barabinofuranosylcytosine (Ara-C) based treatment remains unclear. This study aimed to assess the pharmacogenomic effects of Ara-C metabolic pathway in patients with AML. METHODS:The genotypes of 19 single nucleotide polymorphisms (SNPs) of DCK, CDA and SLC29A1from 100 AML patients treated with Ara-C were examined. All the SNPs were screened with ligase detection reaction assay. The transcription analysis of genes was examined by quantitative real time polymerase chain reaction. The association between clinical outcome and gene variants was evaluated by Kaplan-Meier method. RESULTS:Genotypes of rs9394992 and rs324148 for SLC29A1 in remission patients were significantly different from those in relapsed ones. Post-induction overall survival (OS) significantly decreased in patients with the CC genotype of rs324148 compared with CT and TT genotypes (hazard ratio [HR] = 2.997 [95% confidence interval (CI): 1.71-5.27]). As compared with CT and TT genotype, patients with the CC genotype of rs9394992 had longer survival time (HR = 0.25 [95% CI: 0.075-0.81]; HR = 0.43 [95% CI: 0.24-0.78]) and longer disease-free survival (DFS) (HR = 0.52 [95% CI: 0.29-0.93]; HR = 0.15 [95% CI: 0.05-0.47]) as well As compared with CT and TT genotype, patients with the CC genotype of rs324148 had shorter DFS (HR = 3.18 [95% CI: 1.76-5.76]). Additionally, patients with adverse karyotypes had shorter DFS (HR = 0.17 [95% CI: 0.05-0.54]) and OS (HR = 0.18 [95% CI: 0.05-0.68]). CONCLUSIONS:AML patients with low activity of SLC29A1 genotype have shorter DFS and OS in Ara-C based therapy. Genotypes of rs9394992 and rs324148 may be independent prognostic predictors for the survival of AML patients.

journal_name

J Exp Clin Cancer Res

journal_title

Journal of experimental & clinical cancer research : CR

authors

Wan H,Zhu J,Chen F,Xiao F,Huang H,Han X,Zhong L,Zhong H,Xu L,Ni B,Zhong J

doi

10.1186/s13046-014-0090-9

subject

Has Abstract

pub_date

2014-11-15 00:00:00

pages

eissn

0392-9078

issn

1756-9966

pii

s13046-014-0090-9

journal_volume

pub_type

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SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study.